The influence of inhaled corticosteroids and spacer devices on the growth of respiratory pathogenic microorganisms.

BACKGROUND: Guidelines advise weekly cleansing of spacers, with one of the reasons being to prevent the spacers from becoming colonized with respiratory pathogens. Earlier work in clinical settings showed conflicting results. METHODS: Common respiratory pathogens and Candida albicans were applied on Petri dishes with and without inhaled corticosteroids and in 3 brands of spacer devices, with and without inhaled corticosteroids. Growth was measured. RESULTS: After 24 hours, Staphylococcus aureus grew in 7 of 18 spacers (39%); Pseudomonas aeruginosa grew in 12 out of 18 spacers (67%); and C albicans survived in 5 of 18 spacers (28%). Microorganisms survived on Petri dishes with fluticasone and beclomethasone but not when budesonide was applied. One out of 30 metal Nebuhalers (3%) was colonized after 24 hours, whereas of 30 Volumatics 8 (27%) and Aerochambers, 17 (57%) still had viable microorganisms. Application of inhaled steroids did not affect growth in the spacers. CONCLUSION: The colonization of metal spacers is lower than of spacers made of polycarbonate or polyethylene. C albicans can survive in spacers. The survival of microorganisms in spacers is not influenced by inhaled corticosteroids.

Cigarette smoke extract affects functional activity of MRP1 in bronchial epithelial cells.

Cigarette smoke is the principal risk factor for development of chronic obstructive pulmonary disease (COPD). Multidrug resistance-associated protein 1 (MRP1) is a member of the ATP-binding cassette (ABC) superfamily of transporters, which transport physiologic and toxic substrates across cell membranes. MRP1 is highly expressed in lung epithelium. This study aims to analyze the effect of cigarette smoke extract (CSE) on MRP1 activity. In the human bronchial epithelial cell line 16HBE14o-, MRP1 function was studied flow cytometrically by cellular retention of carboxyfluorescein (CF) after CSE incubation and MRP1 downregulation by RNA interference (siRNA). Cell survival was measured by the MTT assay. Immunocytochemically, it was shown that 16HBE14o(-) expressed MRP1 and breast cancer resistance protein. Coincubation of CSE IC50 (1.53% +/- 0.22%) with MK571 further decreased cell survival 31% (p, = 0.018). CSE increased cellular CF retention dose dependently from 1.7-fold at 5% CSE to 10.3-fold at 40% CSE (both p < 0.05). siRNA reduced MRP1 RNA expression with 49% and increased CF accumulation 67% versus control transfected cells. CSE exposure further increased CF retention 24% (p = 0.031). A linear positive relation between MRP1 function and CSE-modulating effects (r = 0.99, p =0.089) was shown in untransfected, control transfected, and MRP1 downregulated 16HBE14o- cells analogous to blocking effects with MRP1 inhibitor MK571 (r = 0.99, p = 0.034). In conclusion, cigarette smoke extract affects MRP1 activity probably competitively in bronchial epithelial cells. Inhibition of MRP1 in turn results in higher CSE toxicity. We propose that MRP1 may be a protective protein for COPD development.